Human papillomaviruses (HPVs) are common sexually transmitted infections that cause both benign and malignant neoplasms. During the past decade, much progress has been made on the development of prophylactic vaccines with efforts culminating in two proof-of-concept trials showing 100% protection against persistent infection with HPV16 alone or both HPV16 and HPV18. An international phase III trial of an HPV/6/11/16/18 virus-like-particle (VLP) vaccine is currently underway. If high-level efficacy is demonstrated the vaccine could be commercially available within 4 years, at which time, we will know how the vaccine performs up to three and a half years after immunization, but we will not know about long-term efficacy and immunogenicity. The public health benefit of an HPV vaccine will only be realized if protection lasts for more than a couple of years. Furthermore, since first generation prophylactic HPV vaccines will target only 2 to 4 of the 38 different genital HPV types, other prevention strategies will continue to be needed. The purpose of this project is three-fold. First, we plan to collect an additional 3 to 4 years of follow up data on vaccine efficacy among a cohort of women who received HPV16 vaccine, HPV6/11/16/18 vaccine or placebo injections in 1999 or 2000 and were followed with bi-annual examinations through January of 2004. Second, among vaccine recipients, we will evaluate changes over time in both the local and systemic immune response to HPV. And third, we propose to follow a cohort of young women from time of first vaginal intercourse to determine whether consistent and correct condom use with all sex acts and partners decreases a woman's risk of HPV infection. In summary, the long-range goal of this project is to improve the effectiveness of both vaccine-based and behavioral strategies for preventing HPV infection.